For many reasons connected with investigations into the mechanism of chemical and physiological reactions, and more particularly in connection with the manner of action of chemotherapeutic agents in the animal or human body, it is frequently desirable to label organic compounds with isotopes in place of the corresponding atoms originating in nature, that is in place of the atoms containing the natural distribution of isotopes.
Thus, deuterium and tritium, which are isotopes of hydrogen, have found wide application as tracers. The value of such a tracer generally arises from the fact that although its difference in mass (deuterium) or its radioactivity (tritium)--as compared with the regular hydrogen atom--permits its detection, its chemical behaviour is expected to resemble very closely that of the atoms which it has displaced. Notwithstanding that reactions involving the isotopes of hydrogen proceed at slightly but nevertheless measurably different rates, and therefore caution may be necessary in the precise interpretation of investigative results, it is still the case that the chemistry of all the isotopes of hydrogen is basically the same, qualitatively.
A problem which frequently arises in the case of an isotopically-labelled organic compound stems from the fact that the investigator generally desires to be able to trace a labelled atom, which is located in a specific position in the molecular structure. In order to place an isotope in a desired position, it may be necessary to undertake a complicated synthesis, which can be time-consuming and low-yielding, and consequently relatively expensive. Again, where the investigator is concerned with a particular stereoisomer, a difficult separation could be involved, additionally.
The principal object of the present invention is to provide a process by means of which hydrogen atoms in a particular position in a certain class of compounds, may be economically replaced by deuterium or tritium. A further object of the invention is to provide a process for preparing thus-labelled compounds within this class, which are enriched in, or which substantially consist of, a particular geometrical isomer or enantiomer, without requiring any separation of isomers other than that which has already been undertaken in respect of the unlabelled compound. Other objects of the invention will become apparent as the description proceeds.